What is the role of biopsy in the workup of granulomatosis with polyangiitis (GPA)?

Updated: Aug 31, 2021
  • Author: Christopher L Tracy, MD; Chief Editor: Herbert S Diamond, MD  more...
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The diagnosis of GPA is generally confirmed with tissue biopsy from a site of active disease, and renal and lung biopsies are most specific for GPA. However, sampling error may occur, and histopathologic findings can be nonspecific. Tissue diagnosis may not be required if the clinical gestalt is convincing and a site for biopsy is not apparent or would be too invasive to obtain. For example, the finding of leukocytoclastic vasculitis in the setting of pulmonary nodules and PR3-ANCA may be sufficient for the diagnosis.

Renal biopsy may be easier to perform than lung biopsy and has a greater diagnostic yield. The typical renal lesion of GPA is segmental crescentic necrotizing glomerulonephritis with little or no immunoglobulin or complement deposition (pauci-immune). Generally, vasculitis is not observed, but this histology helps in establishing the diagnosis. Renal biopsy findings cannot be used to distinguish between GPA and microscopic polyarteritis. (See the image below.)

A renal biopsy specimen from a 13-year-old girl wi A renal biopsy specimen from a 13-year-old girl with antineutrophil cytoplasmic antibody (C-ANCA)–positive pulmonary renal syndrome. Seven weeks after presenting with sinusitis, she presented with an acute abdomen, pulmonary hemorrhage, and acute renal failure (creatinine 4.9mg/dL). This biopsy specimen shows a necrotizing and crescentic glomerulonephritis (Silver stain).

Although findings on a renal biopsy are often negative for the presence of granulomas in GPA, renal biopsy is nonetheless a very useful diagnostic tool, especially in the setting of pulmonary-renal syndrome.

Importantly, renal biopsy with indirect immunofluorescent staining allows exclusion of anti–glomerular basement membrane (GBM) antibody disease in the setting of a pulmonary renal syndrome. Because of the importance of treating anti-GBM with plasma exchange, this therapy is often started empirically and continued until this disease can be ruled out.

Lung biopsy is performed in the absence of renal involvement by either open or thoracoscopic lung biopsy. Biopsy may reveal the entire histologic spectrum of GPA to include vasculitis and granulomatous inflammation. Chronic infections should be excluded.

In the setting of pulmonary hemorrhage, pulmonary biopsy is much more risky. If the cause of a new infiltrate is unclear, bronchoscopy can be used to confirm the presence of blood. Lavage fluid is bloody and contains hemosiderin-laden macrophages. Stains and cultures should be obtained to rule out infection.

Upper respiratory tract tissue biopsies (nose, sinuses, subglottic region) are frequently nondiagnostic, yielding only nonspecific acute and chronic inflammation in up to 50% of biopsy samples. Upper respiratory tract biopsies demonstrate the full pathologic triad of granulomatous inflammation, vasculitis, and necrosis in only about 15% of cases. However, in the correct clinical context, finding only parts of this triad in an upper respiratory tract biopsy may support the diagnosis of GPA.

Peripheral nerve biopsy can be considered if signs or symptoms such as paresthesias or mononeuritis multiplex are present.

A retrospective study suggested that even in the absence of myalgias or creatine kinase elevation, a muscle biopsy can aid in the diagnosis of systemic vasculitides because biopsy findings can reveal necrotizing or nonnecrotizing vasculitis. [59] A prospective study found that muscle biopsy is a safe method for diagnosing small- or medium-vessel vasculitis, with a sensitivity of 57% overall, and sensitivity of 75% in patients presenting with peripheral neuropathy. [60]

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